Immunohistochemistry for identification of <i>CCND1</i>,<i> NSD2</i>, and <i>MAF</i> gene rearrangements in plasma cell myeloma

<jats:title>Abstract</jats:title><jats:p>The t(11;14)/<jats:italic><jats:styled-content style="fixed-case">CCND</jats:styled-content>1‐<jats:styled-content style="fixed-case">IGH</jats:styled-content></jats:italic>, t(4;14)/<jats:italic><jats:styled-content style="fixed-case">NSD</jats:styled-content>2(<jats:styled-content style="fixed-case">MMSET</jats:styled-content>)‐<jats:styled-content style="fixed-case">IGH</jats:styled-content></jats:italic>, and t(14;16)/<jats:italic><jats:styled-content style="fixed-case">IGH</jats:styled-content>‐<jats:styled-content style="fixed-case">MAF</jats:styled-content></jats:italic> gene rearrangements detected by fluorescence in situ hybridization (<jats:styled-content style="fixed-case">FISH</jats:styled-content>) are used for risk stratification in patients with multiple myeloma (<jats:styled-content style="fixed-case">MM</jats:styled-content>). Compared with conventional <jats:styled-content style="fixed-case">FISH</jats:styled-content> techniques using fresh cells, immunohistochemistry (<jats:styled-content style="fixed-case">IHC</jats:styled-content>) is much more cost‐ and time‐efficient, and can be readily applied to routinely prepared formalin‐fixed, paraffin‐embedded (<jats:styled-content style="fixed-case">FFPE</jats:styled-content>) materials. In this study, we performed tissue <jats:styled-content style="fixed-case">FISH</jats:styled-content> and <jats:styled-content style="fixed-case">IHC</jats:styled-content> employing <jats:styled-content style="fixed-case">FFPE</jats:styled-content> specimens, and examined the usefulness of <jats:styled-content style="fixed-case">IHC</jats:styled-content> as a tool for detecting <jats:italic><jats:styled-content style="fixed-case">CCND</jats:styled-content>1</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">NSD</jats:styled-content>2</jats:italic>, and <jats:italic><jats:styled-content style="fixed-case">MAF</jats:styled-content></jats:italic> gene rearrangements. <jats:styled-content style="fixed-case">CD</jats:styled-content>138 signals were used to identify plasma cells in tissue <jats:styled-content style="fixed-case">FISH</jats:styled-content> and <jats:styled-content style="fixed-case">IHC</jats:styled-content> analyses. With cohort 1 (n = 70), we performed tissue <jats:styled-content style="fixed-case">FISH</jats:styled-content> and subsequently <jats:styled-content style="fixed-case">IHC</jats:styled-content>, and determined <jats:styled-content style="fixed-case">IHC</jats:styled-content> cut‐off points. In this cohort, the sensitivity and specificity for the 3 molecules were ≥.90 and ≥.96, respectively. With cohort 2, using <jats:styled-content style="fixed-case">MM</jats:styled-content> cases with an unknown gene status (n = 120), we performed <jats:styled-content style="fixed-case">IHC</jats:styled-content>, and the gene status was estimated using the cut‐off points determined with cohort 1. The subsequent <jats:styled-content style="fixed-case">FISH</jats:styled-content> analysis showed that the sensitivity and specificity for the 3 molecules were ≥.92 and ≥.98, respectively. <jats:italic><jats:styled-content style="fixed-case">CCND</jats:styled-content>1, <jats:styled-content style="fixed-case">NSD</jats:styled-content>2</jats:italic>, and <jats:italic><jats:styled-content style="fixed-case">MAF</jats:styled-content></jats:italic> gene rearrangements were estimated accurately by <jats:styled-content style="fixed-case">IHC</jats:styled-content>, suggesting that conventional <jats:styled-content style="fixed-case">FISH</jats:styled-content> assays can be replaced by <jats:styled-content style="fixed-case">IHC</jats:styled-content>.</jats:p>